How important are B12 and Folic Acid in treating Schizophrenia?
Schizophrenia has been, for over half a century, associated with poor B12 and poor folic acid status.
B12 and Folic Acid are so important in Schizophrenia because their deficiency predispose schizophrenics to greater difficulty manufacturing neurotransmitters on demand.
These neurotransmitters are needed on demand in brain areas in control of the sensory receipt of information which gets distorted and causes hallucinations and illusions. The outcome of sensory misinformation is further complicated in schizophrenics as other brain areas controlling executive functions (thought processing, planning) are compromised and when bombarded with sensory misinformation the result is psychotic delusional bizzare thought outputs.
B12 and Folic Acid deficiency aspects are best assessed by functional lab measurements of blood homocysteine. High homocysteine levels are detrimental in schizophrenia. The biochemical pathways that get weakened with B12 and folic acid deficiency are the methylation pathways. Methyl donation is a process that allows easier neurotransmitter production on demand. Neurotransmitter production is initiated via methylation processes at the DNA promoter region of brain cells. Adequate methylation is important to all psychiatric conditions including schizophrenia, mood disorder (anxiety, depression, bipolar), behavior disorders (ADD), and neurological disesase.
Our Review on Schizophrenia and our Orthomolecular Treatment Response articles are fully referenced and go into great detail on the assessment and treatment of undermethylation syndromes.
The following abstracts on methylation compromise provide further proof on the need for adequate methylation in schizophrenia. These abstracts look at:
- The correlation between homocysteine, B12, and folic acid lab findings in schizophrenic pathology
- Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms in schizophrenia pathology
- B12 and folic acid recommendations by conventional evidence-based researchers as is applicable in the treatment of schizophrenia
1) Haidemenos A, Kontis D, Gazi A, Kallai E, Allin M, Lucia B. Plasma homocysteine, folate and B12 in chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 15;31(6):1289-96. Epub 2007 Jun 2. 8th Psychiatric Department, Psychiatric Hospital of Attica, 374 Kavalas ave, 12462 Athens, Greece.
Elevated plasma levels of the amino acid homocysteine have been associated with schizophrenia, particularly in young male patients. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. In order to investigate this association, we determined plasma homocysteine, folate and B12 levels in 97 (67 males and 30 females) inpatients with chronic schizophrenia and 103 (46 males and 57 females) controls. Patients and controls did not differ in folate or B12 levels, after adjusting for age. Patients with schizophrenia had higher plasma homocysteine than controls (mean=15.42 micromol/l in cases versus 11.54 micromol/l in controls: F(1,195)=17.978; p<0.001). This difference persisted after controlling for folate and B12 concentrations. Both male and female patients had increased plasma homocysteine compared to controls [(males: mean=16.61 micromol/l in cases versus mean=13.72 in controls: F(1,110)=5.54; p=0.020) (females: mean=12.78 micromol/l in cases versus mean=9.79 micromol/l in controls: F(1,84)=13.54; p<0.001)]. When dividing our sample into two age groups (age < and > or =50 years), both young and older females and younger males with schizophrenia had increased plasma homocysteine compared to controls. We therefore suggest that homocysteinemia is a general risk factor for schizophrenia. We further suggest that it is not limited to young male patients and is not necessarily associated with low folate or B12 levels.
2)Freeman JM, Finkelstein JD, Mudd SH. Folate-responsive homocystinuria and “schizophrenia”. A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity. N Engl J Med. 1975 Mar 6;292(10):491-6.
Homocystinuria and homocystinemia without hypermthioninemia, but with reccurent episodes of folate responseive schizophrenic-like behavior, was documented in a mildly retarded adolescent girl who lacked the habitus associated with cystathionine synthase deficiency. Enzymes involved in homocysteine-methionine metabolism were demonstrated to be normal. A defect in the ability to reducte N-5-10–methylenetetrahydrofolate to 5-methyltetrahydrofolate was demonstrated.Methylenetetrahydrofolate reductase was 18 per cent of control values. Methyltetrahydrofolate is used for the methylation of homocysteine to methionine, and a deficiency of this compound could explain the homocystinemia and homocystinuria.
3) Regland B, Johansson BV, Gottfries CG. Homocysteinemia and schizophrenia as a case of methylation deficiency. J Neural Transm Gen Sect. 1994;98(2):143-52. Department of Clinical Neuroscience, Mölndal Hospital, University of Göteborg, Sweden.
A 27-year-old woman is described whose disorder meets the DSM-III-R criteria for a diagnosis of schizophrenia and who was found to have a significantly increased serum level of homocysteine. Repeatedly, she improved on frequent cobalamin injections and deteriorated in periods without treatment. The effects of prolonged weekly treatment appeared to diminish as time went on, suggesting that the abnormality was not wholly cobalamin-dependent. It was found that methylenetetrahydrofolate reductase (MR) activity in cultured skin fibroblasts was reduced to a magnitude that is found among people with heterozygous deficiency. A defect in MR activity indicates a deficiency in methyltetrahydrofolate (MTHF), with a consequent reduction of the remethylation of homocysteine to methionine. Thus, reduced methylation may explain the increased levels of homocysteine and the transient effects of cobalamin treatment in the patient. Theoretically, MTHF should be the optimal treatment for her. The case reported highlights the importance of assessing the serum homocysteine level in order to detect methylation deficiency in patients with schizophrenia.
4) Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review.Am J Epidemiol. 2007 Jan 1;165(1):1-13. Department of Health Sciences, Alcuin College, University of York, York, United Kingdom.
The authors performed a meta-analysis of studies examining the association between polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, including MTHFR C677T and A1298C, and common psychiatric disorders, including unipolar depression, anxiety disorders, bipolar disorder, and schizophrenia. The primary comparison was between homozygote variants and the wild type for MTHFR C677T and A1298C. For unipolar depression and the MTHFR C677T polymorphism, the fixed-effects odds ratio for homozygote variants (TT) versus the wild type (CC) was 1.36 (95% confidence interval (CI): 1.11, 1.67), with no residual between-study heterogeneity (I(2) = 0%)–based on 1,280 cases and 10,429 controls. For schizophrenia and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.44 (95% CI: 1.21, 1.70), with low heterogeneity (I(2) = 42%)–based on 2,762 cases and 3,363 controls. For bipolar disorder and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.82 (95% CI: 1.22, 2.70), with low heterogeneity (I(2) = 42%)-based on 550 cases and 1,098 controls. These results were robust to various sensitively analyses. This meta-analysis demonstrates an association between the MTHFR C677T variant and depression, schizophrenia, and bipolar disorder, raising the possibility of the use of folate in treatment and prevention.
Tags: anxiety, bipolar, depression, diet, hallucinations, Homocysteine, illusions, mental health, methylation, Methylenetetrahydrofolate reductase (MTHFR), Mood Disorders, neurotransmitter, orthomolecular, psychiatry, psychosis, Schizophrenia, super sensitivity psychosis, treatment and prevention, vitamins
Raymond J. Pataracchia B.Sc. N.D.
These nutritional or biochemical tendencies are relevant to brain health and overall well-being. Diagnosing syndromes reliably is best done by confirming symptoms with targeted lab testing as is described in full on our
clinic website. Alternatively, we encourage prospective clients to fill out our online
nutrient questionnaire to get a snapshot of their biochemical syndrome tendencies.
1. Low Thyroid Metabolism
This common syndrome is often seen with fatigue, poor stamina, poor concentration and constipation. These clients have a slow brain metabolism. When they encounter continuous stresses their thyroid and adrenal glands weaken. Low thyroid function is common in depression, anxiety, psychosis and behavior disorders.
2. Heavy Metal Toxicity
Heavy metals (lead, mercury, cadmium, aluminum, etc.) act as free radicals and can destroy brain tissue. Heavy metals are widespread in our environment and industrial waste and household chemicals are common sources. You may be exposed to the same heavy metal load as others in your family or neighborhood but retain metal more readily if you do not eliminate the metals efficiently (common in slow metabolizers).
3. Copper Toxicity
Copper can be detrimental in excess because it acts as a brain stimulant and can cause paranoia, anxiety and depression and other zinc deficiency symptoms. A significant portion of schizophrenics have dopamine over-stimulation of the frontal cortex. Reducing copper availability can be important for mood and behavior disorders because dopamine can down-regulate the serotonin feel-good neurotransmitter system. Copper is found in dental fillings/appliances and cigarettes. Copper containing animal feed and plant spray (high in a vegetarian diet) infiltrate our food supply. After WWII, homes where built with copper water pipes which leach copper more readily in hard water areas where water softeners are used. Birth control pills increase copper retention and their use has been on the rise since WWII.
4. Under-Methylation
Under-methylated clients basically do not make neurotransmitters on demand. Fatigue and poor concentration is a chief complaint in these clients. This syndrome is more common in patients with a family history of heart disease or strokes. This syndrome is associated with B12 and folic acid deficiency and often has a genetic origin.
5. Poor Digestion
Digestive problems are common. Many people suffer from constipation which results in the toxic build-up of undigested matter and lack of nutrient absorption. It is also common to see people suffering from undiagnosed food intolerances, candidiasis or gastro-intestinal diseases including parasitic infection, IBS, crohn’s and colitis. All of these conditions have specific symptoms the end result of which is the depletion of nutrient minerals, vitamins, fats and proteins. These nutrients are essential building blocks to hormones and neurotransmitters.
6. Protein Deficiency
Most neurotransmitters are made from amino acids obtained from the protein in our diet. Mental health improves when your protein intake is adequate. Many kids and adults are protein deficient because they break down protein too fast (catabolism). North American diets are typically high in carbohydrates and low in protein. The bone matrix is protein dependant.
7. B3 Dependency
These people are so deficient in vitamin B3 that they are dependant on it. Vitamin B3 reduces dopamine overproduction which is common in psychosis and to a lesser extent mood disorders. When excess adrenaline, dopamine and nor-adrenaline are not eliminated properly they break down and oxidize into substances (adrenochrome, dopaminochrome and nor-adrenochrome, respectively) that are similar in structure and action to LSD and mescaline; this ‘adrenochrome hypothesis’ was the first biochemical theory presented in psychiatry as a cause for schizophrenia.
8. Vitamin B6 and Zinc Deficiency
B6 and zinc deficiency are associated with poor mental health, stress intolerance, poor dream recall, acne, white spots on the nails and joint problems. B6 and zinc are involved in the basic protein manufacturing processes of transamination and transcription, respectively. Without adequate B6 and zinc, neurotransmitter manufacture is compromised.
9. Hypoglycemia
Hypoglycemia is a low blood sugar state. Many patients do not eat 3 meals a day and if they do, they eat mainly carbohydrate. Carbohydrate dominant North American diets release sugar to the bloodstream too quickly. Spikes in sugar are followed by sharp drops and the sharper the drop the greater the effect on the brain. Brain cells demand a constant and substantial sugar supply because of their high metabolic rate. A brain starved of its sugar supply is prone to irritability, addiction (sugar, alcohol, etc.) and sometimes criminal behaviour. Hypoglycemic clients are often tired after meals and constantly hungry.
10. EFA Deficiency
Essential fats (EFA’s) are important components of nerve cell walls and are involved in neurotransmitter electrical activity. Sixty percent of the dry weight of the brain is fat. EFA’s are needed to prevent unavoidable oxidative stresses that break down nerve cell membranes. Oxidative stress is associated with reduced mental health. A dopamine rich brain is prone to oxidization and oxidized metabolites can be neurotoxic and hallucinogenic. Heavy metals also cause oxidative stress and destroy brain tissue.
11. Copper Deficiency
Without copper, mood and motivation can be disrupted. Copper is needed for catecholamine neurotransmitter production. Other common copper deficiency symptoms include small cherry red round bulges on the skin (cherry angiomas), frequent bacterial infections, bleeding gums and easy bruising.
12. Vitamin B3 and C Deficiency
Vitamin B3 is one of the few methyl acceptors in the body. As a methyl acceptor, vitamin B3 can limit, in a regulated fashion, neurotransmitter over-production. Vitamin B3 is involved in cellular energy production. Vitamin B3 and C are anti-stress nutrients. Both are also physiological antagonists of copper which is a cofactor in dopamine production. Patients with post-traumatic stress do well on optimal doses of vitamin B3. Patients with a family history of schizophrenia also typically do well on vitamin B3. Vitamin C’s free radical scavenging capability is associated with improved mental health.
13. Magnesium Deficiency
Magnesium deficiency is extremely common. Magnesium deficiency is associated with anxiety, sleep disturbance (problems staying asleep), clumsiness (dyspraxia), depression, muscle cramps/tension of skeletal muscles, blood pressure changes and bladder enuresis. Your bone matrix is magnesium dependant. Too much fiber (phytates) and too few vegetables (magnesium is the central ion in chlorophyll) will deplete magnesium.
14. Calcium and Vitamin D deficiency
Calcium deficiency is common in people with a fast metabolism. Calcium is plentiful in almost all foods. Vitamin D works in the body to maintain calcium levels. Calcium is useful to maintain bone structure. In women under age 40 it can help to restore bone tissue losses. Vitamin D is useful in the formation of the feel good neurotransmitter serotonin. In the winter months when we are exposed to less sunlight our vitamin D levels drop and we get ‘winter blues’. Vitamin D works with thyroid hormone at the cellular level to maintain a high metabolic rate.
15. Iron Deficiency
Iron deficiency is quite common. Iron deficiency symptoms include fatigue, poor attention and cognition, difficulty swallowing pills/food and sallow complexion. Copper toxic patients often exhibit iron deficiency because these minerals are physiological antagonists. Iron deficiency is more common in women due to menstrual blood iron loss. Iron is needed for thyroid hormone production.
Tags: anxiety, bipolar, deficiencies, deficiency, delusions, depression, diagnosis, diet, hallucinations, Homocysteine, mental health, methylation, Mood Disorders, nutrients, nutrition, orthomolecular, psychiatry, psychosis, Schizophrenia, syndromes, treatment and prevention, vitamins
